Biomedical subjects

K Asakura

Publications and source records attributed to K Asakura.

At least 55 records · Page 3Linked to original sources

PubMed1999

Suppressive effects of CTLA4-Ig on nasal allergic reactions in presensitized murine model.

Ag-specific T cell activation requires the engagement of T cell receptor (TCR) with antigen in the context of MHC, and the engagement of appropriate costimulatory molecules. It is well established that B7/CD28-CTLA4 costimulatory pathway plays an important role in the induction of T helper (Th) cells in T-cell dependent immune reactions. In this study, we evaluated the effects of blocking the costimulatory pathway by systemic administration of CTLA4-Ig during repeated nasal antigen challenges in systemically presensitized mouse. The antigen-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine and nasal eosinophilia were significantly suppressed by CTLA4-Ig treatment. Elevation of serum level of antigen-specific IgE, but not IgG1 or IgG2a was inhibited by the treatment. In relation to cytokine levels in the tissue extracts of the nasal mucosa, an up-regulation of IL-4 was significantly inhibited, however, the levels of IL-5 and IFN-gamma were not affected by the treatment. These results suggest that B7/CD28-CTLA4 costimulatory pathway plays an important role in on-going Th2-related allergic reactions in the nose.

Abatacept↗

PubMed1999

A case of anaplastic thyroid carcinoma surviving disease free for over 2 years.

A 52-year female presented with an enlarged thyroid mass and lump sensation in the throat. The cytologic examination showed class five and she was admitted to the hospital to undergo operation. Total thyroidectomy was done and the tumoral invasion of the trachea was removed. We performed tracheoplasty using a sternocleidomastoid muscle-clavicle myoosseous flap in a single stage operation. Histologic diagnosis revealed anaplastic thyroid carcinoma After upper mediastinal dissection had been performed, systemic chemotherapy using pirarubicin, cisplatin and etoposide was administered. In addition, she was treated with radiochemotherapy using pirarubicin, cisplatin and a total of 58 Gy was administered. No recurrence of the tumor has been noted since the above operation 2 years ago. Immunohistochemical studies of primary and metastatic tissues in this case revealed a positive expression of p53 protein in both.

Biopsy, Needle↗

PubMed1999

Chondrosarcoma of larynx: a case successfully reconstructed after total cricoidectomy.

A case of a 64-year-old male with low-grade chondrosarcoma of the left posterolateral lamina of the cricoid cartilage is reported, in which a total cricoidectomy and partial resection of the left thyroid cartilage were performed. The rest of the thyroid cartilage and the arytenoid mucosa were approximated with sutures to the first tracheal ring, and a silastic T-tube was placed through the tracheostoma as a stent. The postoperative course has been successful except for the existence of a tracheal stoma and slight hoarseness. There has been no evidence of laryngeal stenosis nor recurrence at about 9 years postoperatively.

Chondrosarcoma↗

PubMed1999

Internalization and sorting of plasma membrane sphingolipid analogues in differentiating oligodendrocytes.

We studied the formation of early endosomes in differentiating oligodendrocytes and type-2 astrocytes, which are derived from common precursor cells in rat neonates, using fluorescent analogues of lactosylceramide (LacCer) and sulfatide labeled with 4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene++ +-3-pentanoic acid (BODIPY FL C5). These sphingolipid analogues exhibit a concentration-dependent shift in their fluorescence emission maximum from green to red wavelengths that can be used to estimate the relative concentration of an analogue in the intracellular membranes of living cells by quantitative fluorescence microscopy. When oligodendrocytes at various stages of differentiation were incubated with 1 microM BODIPY-sphingolipid at 10 degrees C and washed, yellow/green plasma membrane fluorescence was observed. Quantitative studies confirmed that the amount of BODIPY-LacCer or -sulfatide incorporated into the plasma membrane of a given cell type was identical. When these cells were subsequently warmed to 37 degrees C for 2-10 min to allow internalization to occur, the BODIPY-sphingolipid analogues were distributed in a punctate pattern throughout the cytoplasm. Within individual cells labeled with BODIPY-sulfatide, some endosomes exhibited green fluorescence, whereas others emitted red/orange fluorescence. In contrast, when BODIPY-LacCer was used, only green endosomes were observed. Although this phenomenon could be observed at earlier stages of differentiation, it was most obvious in mature oligodendrocytes, where quantitative measurements of the red/green ratio of individual endosomes suggested about a threefold difference between the concentration of the LacCer and sulfatide analogues in endosomes. These results suggest that "lipid sorting" takes place during endocytosis in mature oligodendrocytes, resulting in selective exclusion of certain lipid species during the internalization process. This sorting event may result in the net addition of lipids to the differentiated oligodendrocyte plasma membrane.

Animals↗

PubMed1999

Role of CD4-positive T cells in the pathogenesis of nasal allergy in the murine model.

BACKGROUND: Antigen-induced upregulation of cytokines, especially Th2-type cytokines, has been proven to be closely related to allergic inflammation in nasal allergy. CD4-positive T cells are supposed to play an important role not only in the induction of allergy but also in allergic inflammation. METHODS: The anti-CD4 mAb was administered to the murine model of nasal allergy either at the beginning of sensitization, just before antigen challenge or during a topical booster sensitization. Then, the effects on the antigen-induced nasal responses and the serum level of antigen-specific IgE antibody were evaluated. RESULTS: When the mAb was applied at the beginning of sensitization, the early-phase nasal symptoms and the late-phase nasal eosinophilia were significantly inhibited, and the 8-day passive cutaneous anaphylaxis (PCA) titer tended to be inhibited. When the mAb was applied just before the challenge, there were no differences in the nasal symptoms, the nasal eosinophilia or the 8-day PCA titer between the mAb-treated animals and the control animals. When the mAb was applied during a topical booster sensitization, the nasal eosinophilia, the 8-day PCA titer and histamine hypersensitivity were significantly suppressed in the treated animals. CONCLUSION: CD4-positive T cells play an important role in the induction of IgE-mediated nasal allergy, occurrence of late-phase allergic inflammation and histamine hypersensitivity, but not in antigen-induced early-phase nasal symptoms in the murine model. In cases of chronic topical antigen exposure, however, the suppressive effects of a single application of the anti-CD4 mAb are not remarkable.

Animals↗

PubMed1999

Topical CTLA4-Ig suppresses ongoing mucosal immune response in presensitized murine model of allergic rhinitis.

Allergic rhinitis is thought to be mediated by CD4+ T cells producing Th2-associated cytokines. Optimal Ag-specific T-cell activation requires the engagement of T-cell receptor with antigen (Ag) in the context of MHC, and the engagement of appropriate costimulatory molecules. One of the most well-characterized costimulatory pathways is the interaction of B7/CD28-CTLA4 molecules. Recent studies have suggested that the costimulatory pathway may influence the development of Th2 immune responses. The objective of this study was the examination of the role of B7/CD28-CTLA4 costimulatory pathway in the pathogenesis of ovalbumin (OVA)-induced immune response in presensitized murine model of allergic rhinitis. Systemically presensitized BALB/c mice significantly developed Ag-induced early phase nasal symptoms, nasal hyperresponsiveness to histamine, nasal eosinophilia, serum levels of OVA- specific IgE and Th2-associated cytokines following repeated topical Ag challenges. Topical administration of CTLA4-Ig during nasal challenges inhibited Ag-induced nasal symptoms and histamine hyperresponsiveness. We also found a significant reduction in nasal lavage eosinophilia and serum levels of OVA-specific IgE. Furthermore, CTLA4-Ig treatment significantly decreased interleukin (IL)-4 content in nasal tissue, while there was no significant change in IL-5 or IFN-gamma levels. These results suggest that B7/CD28-CTLA4 costimulatory pathway mediates the development of ongoing Th2 immune responses and plays a major role in regulating allergic disease, such as allergic rhinitis.

Abatacept↗

PubMed1999

Successful stenting on tortuous coronary artery with accordion phenomenon: strategy--a case report.

Guidewire manipulation through tortuosities is difficult. Straightening a tortuous coronary artery by using a stiff guidewire has been recognized to induce vessel wall shortening referred to as an "accordion phenomenon." With inappropriate identification as dissection or thrombus formation, the risk of performing unnecessary dilation at the pseudo-narrowing site exists. The authors describe here two cases showing the accordion phenomenon induced by a stiff guidewire during successful stenting at a tortuous right coronary artery. In another case, the authors experienced an "accordion phenomenon" at the proximal edge of the Palmaz-Schatz stent implanted in a tortuous right coronary artery. The stent edge was better positioned at the straight portion than at the contour portion in a tortuous coronary artery.

Aortic Dissection↗

PubMed1999

Nonischemic ST-segment elevation induced by negative inotropic agents.

The present study investigated whether regional ventricular dyskinesia (ie, systolic bulging) is a direct cause of ST-segment elevation in canine hearts in vivo. Regional ventricular dyskinesia was induced in 33 anesthetized open-chest dogs by injection of negative inotropic agents into the left anterior descending coronary artery (LAD) without disruption of coronary blood flow. Regional myocardial contraction was assessed in terms of the percent systolic shortening (%SS) and percent systolic bulging (%bulging), which were measured using ultrasonic crystals. The ST-segment elevation of the LAD-perfused area was measured with a unipolar electrode. Lidocaine, a sodium channel blocker, nicorandil, a potassium channel opener, propranolol, a beta-adrenergic blocker, or verapamil, a calcium channel blocker, was administered by intracoronary injection during maximal vasodilation induced by adenosine. All drugs induced dose-dependent ST-segment elevation in association with a parallel reduction in %SS and a parallel increase in %bulging. The absence of myocardial ischemia was confirmed by the absence of NADH fluorescence. It was concluded that regional ventricular dyskinesia had an important role in ST-segment elevation not associated with myocardial ischemia.

Adenosine↗

PubMed1999

Detection of small peripheral lung cancer by digital chest radiography. Performance of unprocessed versus unsharp mask-processed images.

PURPOSE: To clarify whether processed digital chest radiography can improve the detection rate for small peripheral lung cancer. MATERIAL AND METHODS: Five radiologists independently interpreted 54 digitized chest radiographs of 18 patients with small peripheral lung cancers measuring less than 20 mm, which were displayed following 3 types of digital processing: 1) an original version; 2) unsharp mask processing with a type 1 filter (very low-frequency-enhancing, mid-frequency-suppressing, and high-frequency-enhancing filter); and 3) unsharp mask processing with a type 2 filter (very low- and high-frequency-enhancing filter). A total of 1,620 pooled observations were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: The mean area under the ROC curves was 0.68 for the type 1 filter, 0.68 for the type 2 filter, and 0.65 for the unprocessed (original) image. There were no statistically significant differences among these 3 kinds of image processing (p>0.05). In all types of images, the small lung cancer with an alveolar lining tumor growth was less visible than a solid tumor growth (p<0.01); the sensitivity increased with tumor size when the 3 groups of cancers, those measuring less than 10 mm, 11-15 mm, and 16-20 mm, were compared (p<0.01). CONCLUSION: Unsharp mask-image processing of digital chest radiography will not improve the detection rate of small peripheral lung cancer, probably due to a substantial drawback: the limited conspicuity of cancer lesions in the surrounding lung and superposition of structures.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed1999

[Cytokine production of peripheral mononuclear cells in HD-mite-allergic rhinitis patients].

To elucidate the role of cytokines in the pathogenesis of allergic rhinitis, the proliferative response and cytokine production of peripheral mononuclear cells (PMNC) following stimulation with mite-antigen were evaluated in HD-mite-allergic rhinitis patients (mite-allergy group), non-HD-mite pollinosis patients (non-mite-allergy group) and normal subjects (normal group). The proliferative response of PMNC to PHA stimulation was not different among the groups, whereas that to mite-antigen stimulation was significantly higher in the mite-allergy group than in the normal group. Production of both IL-4 and IL-5 from PMNC after stimulation with mite-antigen was significantly higher in the mite-allergy group than in the normal group. Production of IFN-gamma from PMNC after antigen stimulation was significantly increased in both the mite-allergy and normal groups. The ratio of IFN-gamma to IL-4 synthesis was significantly higher in the normal group than in the mite-allergy group. This study revealed cytokine synthesis from PMNC after the antigen-stimulation was predominantly Th2-cytokines in patients with HD-mite-allergic rhinitis.

Animals↗

PubMed1999

[Effects of immunotherapy on cytokine production from peripheral blood mononuclear cells in patient with house dust mite allergic rhinitis].

We studied effects of immunotherapy on mite antigen-induced cytokine production from peripheral blood mononuclear cells in patient with house dust mite allergic rhinitis. In good response group, IL-4 production were lower than that of poor response group. In contrast, IFN-gamma production and the ratio of IFN-gamma to IL-4 synthesis were significant higher than that of poor response group. The production of IFN-gamma significantly correlated with the periods of immunotherapy. These results suggest that the changes of cytokine synthesis have a close relationship to clinical effects of immunotherapy.

Adult↗

PubMed1999

Stretch-activated ion channel blocker gadolinium attenuates ischemic ST-segment elevation in canine myocardium.

Regional transmural ischemia causes both ST-segment elevation and systolic elongation (bulging) of the myocardium. Mechanical stretch might alter the transmembrane potential via stretch-activated ion channels (SAC); however, the role of SAC on ischemic ST-segment elevation has not yet fully studied. The present study investigated the role of SAC in the genesis of ischemic ST-segment elevation in the in-vivo canine heart. In 6 anesthetized dogs, an extracorporeal conduit connected to the left anterior descending coronary artery was occluded for 5 min before and after the intracoronary infusion of gadolinium (Gd, 500 micromol/min). To eliminate the effect of ischemic preconditioning, the bypass was occluded for 5 min before the experiment. Percent systolic shortening (%SS) and percent systolic elongation (%bulging) were measured using a pair of ultrasonic dimension crystals. A unipolar epicardial ECG was monitored at the center of the ischemic area for the measurement of the ST-segment level. At the end of coronary occlusion, there was no difference in the reduction of %SS or the increase of %bulging between before and after infusion of Gd. ST-segment elevation, however, was significantly attenuated by the infusion of Gd. These data demonstrated that the activation of SAC is one cause of ischemic ST-segment elevation.

Animals↗

PubMed1999

[A relationship between birch pollen and meteorological factors during the past four years and pollen survey in Sapporo in 1997].

It is well known that grass pollinosis has been the most representative pollinosis in Hokkaido prefecture, Japan, However, it is also well known that birch (Japanese white birch, Betula platyphylla var. japonica) pollinosis is gradually increasing, which is marked especially in Sapporo and its neighborhood. We analyzed a relationship between the birch pollen count and meteorological factors statistically. Moreover, the principal airborne pollen counts in Sapporo in 1997 were assessed and compared with the previous pollen data. As a results of this study, it was showed a close relationship between the annual amounts of birch pollen and meterological factors of the year before, especially in May and June might be important. Moreover, there is a strong negative correlation between the birch pollen count and humidity, which seems to affect bringing up flower buds. As for the principal airborne pollen counts, some kinds of tree pollen, including birch pollen, were observed from the end of March, followed by grass (Gramineae) pollen in June and mugwort (Artemisia) pollen from the end of August, respectively. The annual amounts of grass pollen showed a decreasing trend.

Air Pollution↗

PubMed1999

Angioplasty/bypass combination therapy in an 89-year-old man with left main trunk disease.

We report a case of an 89-year-old man presenting with unstable angina and left main trunk disease. Minimally invasive direct coronary artery bypass grafting supplemented by catheter intervention was successfully performed. In view of the increasing elderly population, angioplasty/bypass combination therapy may be an important alternative for elderly coronary artery disease patients.

Aged↗

PubMed1998

Differentiation-specific mRNA expression of a mouse bipotential glial cell line.

We have previously reported that a bipotential glial cell line from mouse cerebrum, designated OS3, phenotypically differentiates into oligodendrocytes and astrocytes both in vitro and in vivo. To study the potential mechanisms of differentiation, in this study we investigated mRNA expression of cytokines and developmentally regulated proteins in OS3 during differentiation into oligodendrocytes by semi-quantitative reverse transcription and polymerase chain reaction. In the presence of 10% calf serum OS3 cells expressed IL-1alpha and IL-1beta mRNA. However, when the cells were cultured in chemically defined medium or low serum-containing medium the expression of IL-1alpha and IL-1beta mRNA was down-regulated. Under stimulation of phorbol ester, expression of IL-6 and nerve growth factor mRNA was up-regulated. The capacity for differentiation of OS3 cells into oligodendrocytes in vitro was limited and most OS3 cells ceased their differentiation at the proligodendroblast stage. However, expression of proteolipid protein (PLP) and DM20 mRNA was detectable and was up-regulated in accordance with the differentiation into oligodendrocytes. As a control, primary astrocytes expressed DM20 mRNA but not PLP mRNA and the expression of DM20 mRNA was independent of culture condition. Therefore, OS3 cells will be of use for the study of differentiation of progenitor cells into type-2 astrocytes or oligodendrocytes at the molecular level.

Animals↗

PubMed1998

Targeting of IgMkappa antibodies to oligodendrocytes promotes CNS remyelination.

We previously identified the remyelinating activity of a natural IgMkappa oligodendrocyte-reactive autoantibody (SCH94.03), using a virus-induced murine model of multiple sclerosis. We now describe a second mouse IgMkappa monoclonal antibody (mAb) (SCH79.08) raised against normal mouse spinal cord homogenate, which reacts with myelin basic protein and also promotes remyelination. Because these two mAbs recognize different oligodendrocyte antigens, several previously identified oligodendrocyte-reactive IgMkappa mAbs (O1, O4, A2B5, and HNK-1), each with distinct antigen specificities, were evaluated and found to promote remyelination. In contrast, IgMkappa mAbs that did not bind to oligodendrocytes showed no remyelination. One of these, CH12 IgMkappa mAb, which shares variable region cDNA sequences with SCH94.03 except for amino acid differences in the complementarity-determining region 3 in both heavy and light chains, did not bind to oligodendrocytes and did not promote remyelination. The fact that multiple oligodendrocyte-reactive antibodies with distinct antigen reactivities induce remyelination argues against direct activation by a unique cell surface receptor. These findings are most consistent with the hypothesis that the binding of mAbs to oligodendrocytes in the lesions induces myelin repair via indirect immune effector mechanisms initiated by the mu-chain. Importantly, these studies indicate that oligodendrocyte-reactive natural autoantibodies may provide a powerful and novel therapeutic means to induce remyelination in multiple sclerosis patients.

Animals↗

PubMed1998

The effect of adenotonsillectomy in children with OSA.

Adenotonsillar hypertrophy and abnormal facial morphology are thought to be important for the occurrence of obstructive sleep apnea syndrome (OSA). We evaluated the effects of adenidectomy and/or tonsillectomy and the relationship between the treatment results and facial morphology in 134 children with OSA. Significant improvements in apnea-hypopnea indes (AHI) and lowest blood oxygen saturation (SaO2) were noted and 78.5% of the patients improved after adenoidectomy and/or tonsillectomy. Additional operations were needed in two out of 13 cases of the adenoidectomy group and two out of four cases of the adeno-monotonsillectomy group. In the adenotonsillectomy group, the unimproved children tended to have smaller tonsils, narrower epipharyngeal airspace, and more poorly-developed maxillary and mandibular protrusion than the improved children.

Adenoidectomy↗

PubMed1998

Polymorphism in the Ialpha1 germ-line transcript regulatory region and IgA productivity in patients with IgA nephropathy.

Enhanced in vivo and in vitro production of IgA has been reported in patients with IgA nephropathy (IgAN) and their family members. It is generally considered that IgA1 is a prominent subclass of IgA in IgAN. Although genetic mechanisms of IgA class switch recombination in IgAN have been studied enthusiastically, the critical factors that induce IgA1-specific class switching in IgAN have yet to be elucidated. A large body of data indicates that the germ-line transcript of Ig constant region (C(H)) genes that precedes actual class switching has regulatory effects on class switch recombination. To analyze structural abnormalities in the Ialpha1 germ-line transcript regulatory gene, a region about 1000 bp long located upstream of Ialpha1 exons was surveyed by the PCR-single strand conformation polymorphism method, and the polymorphism detected was confirmed by subsequent DNA sequencing. Three hot spots for point mutation were detected upstream of the promoter region of the Ialpha1 germ-line transcript, and the mutations were observed more frequently in patients than in controls. Patients with the mutations showed higher levels of serum IgA and higher in vitro IgA synthesis. In the luciferase assay, the regulatory gene with the mutations showed a potent effect for induction of the Ialpha1 germ-line transcript. The polymorphism in the Ialpha1 regulatory region possibly causes enhanced IgA production in some patients with IgAN.

Base Sequence↗